Improving Neonatal Outcomes with Human Milk

Report
Roger G. Faix, MD
Division of Neonatology
University of Utah
Primary Children’s
Intermountain Medical Center
0
DISCLOSURE
The content of this
presentation does not
relate to any product in
which I have a financial
interest or potential conflict
of interest.
Learning Objectives
1- Learn why breast milk is the recommended form of
enteral nutrition for all infants.
2- Learn how commercial formulas differ from human
breast milk.
3-Appreciate longitudinal and other changes in content
of human breast milk.
Got
Milk?
Got
Breast
Milk?
Breastfeeding and Use of Human Milk
Policy Statement. Pediatrics 2012;129:e827-841
 Breastfeeding and use of human milk confer unique
nutritional and non-nutritional benefits to infant and
mother and, in turn, optimize infant, child, and adult health
as well as child growth and development.
 Recently published evidence-based studies have confirmed
and quantitated risks of not breastfeeding.
Infant feeding should not be considered as a lifestyle
choice but rather as a basic health issue.
Improving Outcomes with Human
Milk
Lifestyle Choices
 Have a family
 Have a career
 Have a snowmobile
Basic Health Issues
 Deliver in a hospital
 Immunize your baby
 Use a car seat
 Infant feeding
(breast milk)
Improving Outcomes with Human
Milk in the Nursery and NICU
Provider Choices
 Switch ventilators
 Order a β-natriuretic
peptide assay
 Be nice to residents
Basic Health Issues
 Treat respiratory failure
 Treat sepsis
 Be nice to staff
 Infant feeding
(breast milk)
Meinzen-Derr J, et al. Role of human milk in extremely low birth
weight infants’ risk of necrotizing enterocolitis or death.
J Perinatology 2009;29:57-62
o
NEC (7.7%) or death > 14d, 173/1272(13.6%)
Each 100 ml/kg
increase in HM
intake during the
first 14 d was
associated with
decreased risk of
NEC or death.
(HR 0.87 (95% CI
0.77, 0.97)
Ronnestadt A, et al. Late-onset sepsis in a Norwegian national
cohort of extremely premature infants receiving very early
human milk feedings. Pediatrics 2005;115:e269
o
80/405 LOS (23%)
Feedings
started at 1-2
mL q2-3h
within a few
hours of
delivery and
advanced 0.51 mL q 6-8h
Survival free from LOS
according to week when full
feedings established
RR of LOS if full feedings
not established within a
certain age (days)
92% MM
6% donor
Infectious Diseases Influenced by Infant Diet
Infants - Children
Pediatrics 2012;129:e827-841
Diseases and Conditions influenced by Infant Diet
Pediatrics 2012;129:e827-841
Basic Nutrients
Proteins
Fats
Carbohydrates
Vitamins
Minerals
Water
All are present in milk of all species, but types and
proportions vary by species, making each specific
and apparently uniquely suited
Breast milk is more than good nutrition
Milk Protein
Species Specific Content
Protein
Human Milk
Cow’s Milk
Quantity
Low
3-4X Higher
Type
Whey predominant
Casein predominant
Digestibility
Curds soft, easy to digest
Curds rubbery, harder to
digest
Brain and Eye
development
Taurine present
Taurine absent
Bioactive proteins
Present
Present
Calves are mostly muscle and bone. They double their weight
in <50 days. Humans are designed to grow more slowly, with emphasis
on brain growth and social development.
A Partial List of Protein Functions
New Peptide Derivatives Continue to be Discovered
There are 268 proteins in
human milk from which
even more bioactive
peptides are released.
Though some proteins are
common to both species,
they occur in significantly
different quantities.
Hetinga K et al. The Host Defense Proteome of Human
and Bovine Milk. PLoS One. 2011;6(4):e19433
“The expression of genes can be
altered by changing the molecular
environment that cells inhabit . . .
no single act alters the environment
of the cells of the body more than
the ingestion of food.”
Sanderson, IR. Dietary Regulation of Gene Expression.
Gastroenterology and Nutrition, Saunders, 2008, p28
Gut Transformation after Birth
Walker A, J Pediatrics 2010; 156:S3-7
o
→
FETUS at birth
Sterile GI tract
Immature epithelium
Delayed enterocyte proliferation
Sparse lymphoid cells
Breast fed NEONATE
Bacterial colonization (2-3 hr)
Proliferating epithelium
All subclasses of enterocytes
Abundance of lymphoid tissues
Greater Enterocyte Proliferation with
Colostrum than with Mature Breast Milk
o
Proliferation of enterocytes as measured by the incorporation of
3H-thymidine after exposure to early (3d) or late (57d) breast milk.
Tapper et al. J Pediatric surgery 1979;14:803-8
“If peptides derived from gastrointestinal
digestion of dietary proteins play a specific
role as metabolic or physiological regulators,
it seems logical that the biological activity
exerted in the newborn by infant formulas or
breast milk could be different.”
Hernandez-Ledesma B, et al.
Interntl Dairy Journal 2007;17:42-49
Colostrum is Part of Transition
Constituent
Colostrum
1-5 d
Mature BM
> 30 d
Lysozyme (g)
218
161
Lactoferrin (g)
330
167
IgA (g)
364
142
1) Colostrum (Birth-4d) is high in protein, fat-soluble vitamins,
minerals, and immunoglobulins. It is different because
normal transition requires it.
2) Transitional milk (2d-2wks) includes high levels of fat, lactose,
water-soluble vitamins, and contains more calories than colostrum
Composition of Cow Milk formulas
Based on nutrient content of human milk at 1-3 mo
o Protein: nonfat bovine milk and whey concentrate
o Fat: blend of vegetable oils
o Carbohydrate: corn syrup solids and lactose
o Vitamin and mineral mix
o Additional ingredients are manufacturer-based:
iron (1959), taurine (1984), DHA (2000), leutein (2012)
Content is regulated by the FDA and is based on
the AAP Committee on Nutrition recommendations
Milk Protein
o
Protein
Human Milk
Cow’s Milk Formula
Quantity
Low
3-4X Higher
Type
Whey predominant
Casein predominant
Digestibility
Curds soft, easy
More intolerance
Bioactive proteins
Species-specific
differences associated
with better outcomes
Different in many ways
Human milk protein is not ‘merely for nutrition.’ It displays
medicinal qualities that initiate and modulate development
resulting in profound effects on infant survival and health
Milk Fat
Species Specific Content Differences
Fat
Human Milk
Cow’s Milk Formula
Content during feeding
Low → High
Constant
Content if feed frequently
High
Constant
Digestibility
Lipoprotein
Bile Salt-stimulated lipase
No Lipases
Essential FA
6-10 times Higher
Lower
ARA, DHA (brain/eye)
Present
Recent additives
Breastfeeding is associated with improved
child cognitive development.
MA Quigley et al. J Pediatrics 2012;160:25-32
Preterm Lipid Study
Pediatrics 2001;108:359 –371
“Whether or not formulas designed for the premature
infant should be supplemented with long-chain PUFA,
including arachidonic acid and docosahexaenoic acid has
become one of the most controversial issues in infant
nutrition today . . .”
“. . . Several lines of logic suggest that premature infants
fed formulas without AA and DHA may be at increased
risk of slower development related to suboptimal blood
and tissue levels of these fatty acids compared with the
term infant.”
Milk Carbohydrate
Breast Milk is not just Lactose
 Oligosaccharides - nonnutritive, the third most common solute
in human milk after lactose and fat. Cow’s-milk formulas
contain very little.
 Prebiotic agents that encourage the growth of beneficial (probiotic)
organisms
 Anti-infective in the intestinal, respiratory and urinary tracts. >130
identified pathogen-specific, binding (decoy) inhibitors
 Functional components of brain gangliosides essential to nerve cell
transmission, memory formation and cell-to-cell communication.
Miller JB. Invited Commentary: Human milk oligosaccharides: 130 reasons to
breast-feed. British Journal of Nutrition 1999;82:333–335
Ballard O and Morrow A. Human Milk Composition. PCNA 2013;60(1)49-74
Milk Vitamins and Minerals
Species Specific Content Differences
 All vitamins and minerals in human milk have a higher
bioavailability than in cow milk formula
 50-75% of Fe in BM is absorbed compared to 4% in formula
 To compensate, more is added to formula:
Fe
(mg/L)
HM (T)
HM (PT)
HM (PT)
+HMF 1
0.3-0.9
1.21
4.58
HM (PT) +
HMF 2
PF1 - 24
PF2 - 24
15.6
14.61
14.6
Excess, unabsorbed minerals (especially iron) alter gut flora
and facilitate growth of potentially harmful bacteria
Vitamin and Mineral Supplementation
Pediatrics 2012;129:e827-e841
 Vitamin K 0.5 to 1.0 mg IM after the first feeding at
breast and before 6 hours
 Vitamin D 400 U/day PO at hospital discharge
 No Fluoride during the first 6 months and thereafter
only if [fluoride] < 0.3 ppm
 Iron orally before 6 months if low iron stores
Premature infants need multivitamins and iron until
ingesting a mixed diet and growth is normalized
Optimal Source of Nutrients
Breast milk content is essential for optimal development
 Basic nutrient and bioactive component content and
proportions are species specific. Many differences exist.
 Breast milk content can be (and is) altered by individual needs
and circumstances. Formula content is fixed.
 Formula is not milk. Many components are missing. Content
is further altered by pasteurization.
What formula lacks or has in it can make a difference
Term vs Preterm Milk Content
Nutrient/L
Term
Preterm
Vitamins
Term
Preterm
Cal/oz
19.5-21
20.1
Vit A, IU
2252
3899
Protein, g
9
14.09
Vit D, IU
20
20
Fat, g
39.05
38.93
Vit E, IU
4.1
10.7
Carb, g
79
66.4
Vit K, mcg
2-3
2
Calcium, mg
200-250
248
Iron, mg
0.3-0.9
1.21
Sodium, mg
120-250
248
Zinc, mg
1-3
3.42
mOsm/L
257
255
Composition of human milk varies with maternal diet, lactation stage, within
feedings, diurnally, and among mothers. Pediatric Nutrition Handbook 2009
Morton J, et al. Combining hand techniques with electric
pumping increases the caloric content of milk in mothers of
preterm infants J Perinatol 2012;32:791-796
o
Frequency of hand
expression in first 3d
Group I < 2 times/day
Group II 2-5 times/day
Group III > 5 times/day
Increased frequency of hand expression in first 3d
increases milk production.
Formula content
Neofax 2011, 24th Edition
Nutrient/L
Term Milk
Preterm
PF-1 20
Cal/oz
19.5-21
20.1
20
Protein, g
9
14.09
20
Fat, g
39.05
38.93
36.7
Carb, g
79
66.4
69.7
Calcium, mg
200-250
248
1217
Iron, mg
0.3-0.9
1.21
12.2
Sodium, mg
120-250
248
291
Zinc, mg
1-3
3.42
10.1
Because of poorer bioavailability, more is often needed
Vohr B, et al. Beneficial effects of breast milk in the neonatal intensive
care unit on the developmental outcome of extremely low birth
weight infants at 18 months of age. Pediatrics 2006;118(1)
no BM
< 20th
20-40
40-60
60-80
> 80th
p
BM (ml/kg) qd
0
1
7
24
64
111
-
BM @ discharge
0
22
45
67
95
124
Mean MDI
76
74
77
78
80
87
.004
Mean PDI
81
81
83
84
84
89
.003
BRS percentile
46
45
52
50
52
59
.028
Rehosp < 1y
30
25
32
26
23
13
.046
No diff BW, GA, sex, IVH gr 3-4, PVL, NEC, sepsis, BPD, LOS, CP, blindness,
hearing loss, weight and OFC @ 18 mo. Adj for mom age, edu, race, income
For every 10 ml/kg/d increase in BM, there was an increase in MDI
(0.53 points), PDI (0.63 points), BRS (0.82 %ile), and a decreased
likelihood of re-hospitalization (6%)
Vohr B, et al. Persistent beneficial effects of breast milk ingested
in the neonatal intensive care unit on outcomes of extremely low
birth weight infants at 30 months of age. Pediatrics 2007;120(4)
o
The principal effects of BM in children at 30
months CA are on cognition and behavior.
Cost to Use
Breast milk (no cost)
PF1 ($1.18/oz)
Expressed ($15/mo pump)
Elemental 1 ($1.77/oz)
Donor ($3.50/oz + freight)
Elemental 2 ($2.48/oz)
Commercial ($30.00/oz)
HMF/packet ($1.08-1.50)
Cost to Not Use Breast Milk
 If 90% of US families followed guidelines to BF exclusively for 6 mo,
the US would annually save $13 billion from reduced medical and
other costs. Bartick, M. Pediatrics 2010;125:e1048-e1056 (2007 dollars)
CDC
Start
Any BF
6 mo
Any BF
12 mo
Exclusive
3 mo
Exclusive
6 mo
US
74%
43%
21%
32%
12%
Utah
90%
60%
26%
43%
17%
Healthy People 2010
75%
50%
25%
40%
17%
2012 AAP Policy
90%
 Health care costs for newborns are three times lower for babies
whose mothers participate in the company’s employee maternity
and lactation program. www.surgeongeneral.gov/topics/breastfeeding/
Ganapathy V, et al. Breastfeeding Med 2012;7(1):29-36
COSTS for extremely premature infants
Supplements/infant
BOVINE
HUMAN
195
10,321
Baseline Hospitalization (EP, no NEC)
207,378
207,378
Medical NEC ($74,004/EP infant)
11,798
1,798
Surgical NEC ($198,000/EP infant)
12,583
1,798
$ 231,954
$ 223,787
TOTAL
Net Savings per EP Infant Admitted
$ 8,167*
( *p<0.0001, 95% confidence interval, $4,405–$11,930)
“The analyses presented in this article may assist
healthcare providers and institutions to justify an
increased use of human milk and human milk products to
promote better health outcomes in EP infants.”
Ziegler EE. Meeting the Nutritional Needs of the Low-BirthWeight Infant. Ann Nutr Metab 2011;58(suppl 1):8-18
Growth failure is associated
with impaired neurocognitive
development
Human milk must be fortified
with nutrients in order to
enable adequate growth
Parameter
500-700
700-900
900-1200
1200-1500
Fetal wt gain (g/kg/d)
21
20
19
18
Protein (g/kg/d)
4.0
4.0
4.0
3.9
Energy (kcal/kg/d)
105
118
119
127
When growth of preterm infants lags behind expected
growth (that is, growth like the fetus), it is almost always
protein that is limiting growth
Carlson SJ, Ziegler EE. Nutrient intakes and growth of very low
birth weight infants. J Perinatol 1998; 18: 252–258.
Olsen IE, et al. Intersite differences in weight growth velocity of
extremely premature infants. Pediatrics 2002; 110: 1125–1132.
Embleton NE, Pang N, Cooke RJ. Postnatal malnutrition and
growth retardation: an inevitable consequence of current
recommendations in preterm infants? Pediatrics 2003; 107:
270–273.
Arslanoglu S, Moro GE, and Ziegler EE. Adjustable fortification of
human milk fed to preterm infants: does it make a difference?
J Perinatology 2006;26:614-621
o
End Point 2000 g
16
14
8
bovine whey protein concentrate
Arslanoglu S, Moro GE, and Ziegler EE. Adjustable fortification of
human milk fed to preterm infants: does it make a difference?
J Perinatology 2006;26:614-621
o
Optimal Intakes:
3.4
2.8
Intrauterine
protein intake of
fetuses weighing
the same as the
mean body
weights of study
infants for each
week.
Arslanoglu S, Moro GE, and Ziegler EE. Preterm infants fed
fortified human milk receive less protein than they need.
J Perinatology 2009;29:489-492
Variable
Adjusted
Assumed Actual
Standard
Assumed Actual
Protein content (g/dL)
2.8
2.3
2.3
1.9
Fat content (g/dL)
3.9
3.6
3.9
3.4
Kcal/dL
90.5
85.2
85.0
80.5
Protein intake (g/kg/d)
4.2
3.4
3.5
2.8
kcal/kg/d
136
128
128
121
The inadequate levels of actual protein intakes observed in the
present study offer an explanation of why preterm infants fail to
grow adequately in spite of receiving adequate energy intakes.
Wojcik KY, et al. Macronutrient Analysis of a Nationwide Sample
of Donor Breast Milk. J Am Diet Assoc 2009;109:137-140
415 samples from 273 donors nationwide
Nutrient/L
Mature Milk
Donor Milk*
kcal/oz
20
19.2 (11-32)
Protein, g/dL
1.0-1.2
1.2 (0.7-2.1)
Fat, g/dL
variable
3.2 (0.7-7.1)
Carb, g/dL
-
7.8 (4.9-12.7)
*majority mature milk, but also a “sizable amount” of premature
milk, 65% < 20 kcal/oz and 35% > 20 kcal/oz
** Ziegler EE. Ann Nutr Metab 2011;58(suppl 1):8-18
Human milk protein, fat and energy content may be lower
Effect of breastfeeding vs formula feeding
on
childhood obesity
j
Arenz et al.,Int J Obes Relat Metab Disord 2004;28:1247-1256
The mechanisms for the association between
breastfeeding and obesity are unclear
De Onis M, et al. Global prevalence and trends of overweight
and obesity among preschool children. Am J Clin Nutr
2010;92(5):1257-64
o
16.00%
14.00%
12.00%
10.00%
Developed
8.00%
Global
6.00%
4.00%
2.00%
0.00%
1
2
3
4
5
6
7
1990
1995
2000
2005
2010
2015
2020
Children age 0-5 years
> 2SD weight for height median
Standards for Normal Growth have Changed
www.cdc.gov/growthcharts/
8000 Infants
“All young children
have the potential
to grow similarly,
regardless of their
ethnic group or
place of birth, if
they are in a healthy
environment and
receive adequate
nutrition.”
Characteristics and Potential Functions
of Human Milk Adiponectin
 Protein hormone produced by adipose tissue which
enhances fatty acid metabolism and reduces
inflammation
 Low levels are associated with obesity, type 2 diabetes,
dyslipidemia, and cardiovascular disease
 Higher levels in human milk are associated with lower
infant weight in the first 6 months of life in BF infants and
may attenuate inflammatory processes
Newburg DS et al. J Pediatr 2010;156:S41-6
Adequate Growth
Summary
• Historically, preterm infants gain weight faster on formula
than on human milk (breast or donor).
• Because protein and energy content of human milk vary,
more than standard fortification may be needed to
achieve short-term growth standards.
• However, faster early growth may be associated with
higher rates of obesity. Growth norms (mostly formulafed infants) are too high.
• Despite slower growth, breastfed infants have better
neurodevelopmental outcomes.
Consider these Suggestions:
What % of your NICU infants receive all BM to discharge?
 Make lactation support a part of parent interactions
 Educate all mothers on the value of human milk
 Explain the need for breastfeeding mothers to pump and
express milk early and often (8-12 times daily)
 Know they are doing it and doing it effectively
 Strongly encourage exclusive human milk feedings (as
you would treatment for presumed sepsis)
Fewer than 11%
of US working
parents receive
paid leave when
a child is born
Providing up to 12 weeks unpaid leave only applies to
companies with 50 or more employees
Human Milk Banking Association
of North America www.hmbana.org
o
Milk Bank Donor Requirements
 In good health.
 Non-smoker. No use of any Nicotine products.
 Negative blood test for viruses (Prenatal results are NOT
used).
 Using no medications during the time milk is collected for
donation, except for: vitamins and minerals; food
supplements, progestin-only birth control, or replacement
hormones: thyroid, insulin
 Limited use of caffeine; and a waiting period is required
after alcohol use before donating milk
 Willing to donate a minimum of 150 ounces total during
the time they are a donor
How is Donor Milk Processed?
http://www.milkbankcolorado.org/
o
Milk from 3-5 donor
mothers is thawed,
transferred to glass
flasks, and mixed.
How is Donor Milk Processed?
http://www.milkbankcolorado.org/
j
 Milk samples are
cultured during the
pasteurization
process then frozen
at -4°F and stored
 Culture-positive milk
is discarded
•
Milk is shipped frozen
overnight to hospitals
and individuals
Types of Donor Milk Available
 Early Full Term: from first 7-10 days post partum - 2 oz bottles
(when available)
 Preterm: for infants under 1500 grams and/or less than 36
weeks gestation - 2 oz bottles (when available)
 Full Term: (20 cal or higher) for infants at or over 36 weeks
gestation - 4 oz bottles (Also used routinely for premies when
preterm not available )
 Non-fat: for chylothorax therapy (0.0 - 0.3% fat) - 2 oz bottles
Each Batch is also Analyzed for Macronutrient Content

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